Across-Species Scaling of Monoclonal Antibody Pharmacokinetics Using a Minimal PBPK Model.

ABSTRACT:

Purpose

To examine the across-species scalability of monoclonal antibody (mAb) pharmacokinetics (PK) and assess similarities in tissue distribution across species using a recently developed minimal PBPK (mPBPK) model.

Methods

Twelve sets of antibody PK data from various species were obtained from the literature, which were jointly and individually analyzed. In joint analysis, vascular reflection coefficients for tissues with either tight (σ 1 ) or leaky endothelium (σ 2 ) were assumed consistent across species with systemic clearance allometrically scaled (CL = a∙BW (b) ). Four parameters (σ 1 , σ 2 , a, and b) were estimated in the joint analysis. In addition, the PK from each species was individually analyzed to assess species similarities in tissue distribution.

Result

SUBMITTER: Zhao J 

PROVIDER: S-EPMC4580522 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature